The Role of GITR/GITRL Interaction in Autoimmune Diseases

Tian, Jie; Zhang, Beibei; Rui, Ke; Wang, Shengjun

doi:10.3389/fimmu.2020.588682

Cited by 54 publications

(43 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the CD137/CD137L interaction not only constitutes a costimulatory signal triggering the expansion of the CD4 + and CD8 + T cells, but also amplifies the inflammatory responses mediated by NK cells [ 61 ]. Our results also showed that MIM tends to increase the expression of GITRL on the HUVEC surface ( Figure 5 ), which may potentially facilitate GITR/GITRL signaling and thus result in T cell activation and proliferation [ 62 ]. Indeed, numerous studies using suboptimal preprimed anti-CD3 stimulated T cells reported the role of the GITR/GITRL axis as a costimulation signal for the T cells [ 63 ].…”

Section: Discussionmentioning

confidence: 81%

The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses

Jacques¹,

Chatelais²,

Fekir³

et al. 2021

IJMS

View full text Add to dashboard Cite

This study aimed at evaluating the effects of the micro-immunotherapy medicine (MIM) 2LEID, both in vitro and in vivo, on several components of the innate and adaptive immune system. MIM increased the phagocytic activity of macrophages, and it augmented the expression of the activation markers CD69 and HLA-DR in NK cells and monocytes/macrophages, respectively. The effect of MIM was evaluated in a model of respiratory infection induced by influenza A virus administration to immunocompetent mice in which it was able to improve neutrophil recruitment within the lungs (p = 0.1051) and slightly increased the circulating levels of IgM (p = 0.1655). Furthermore, MIM stimulated the proliferation of CD3-primed T lymphocytes and decreased the secretion of the immunosuppressive cytokine IL-10 in CD14+-derived macrophages. Human umbilical vein endothelial cells were finally used to explore the effect of MIM on endothelial cells, in which it slightly increased the expression of immune-related markers such as HLA-I, CD137L, GITRL, PD-L1 and ICAM-1. In conclusion, the present study suggests that MIM might be a promising nonspecific (without antigen specificity) immunostimulant drug in preventing and early treating respiratory infections, but not only exclusively, as it would gently support several facets of the immune system and host defenses.

show abstract

Section: Discussionmentioning

confidence: 81%

The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses

Jacques¹,

Chatelais²,

Fekir³

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…(Supplementary Figure 1 ). The elevated GITRL or IL-4 have been thoroughly studied in RA and associated with disease severity linked to Th17-cell activation or autoantibody induction, respectively [ 16 , 17 ]. However, their association with the increased concentration with PYY (3-36) needs further mechanistic studies to explain.…”

Section: Resultsmentioning

confidence: 99%

Investigation of Newly Diagnosed Drug-Naive Patients with Systemic Autoimmune Diseases Revealed the Cleaved Peptide Tyrosine Tyrosine (PYY 3-36) as a Specific Plasma Biomarker of Rheumatoid Arthritis

Balog

Kemény

Puskás

et al. 2021

Mediators of Inflammation

View full text Add to dashboard Cite

There is a current imperative to reveal more precisely the molecular pathways of early onset of systemic autoimmune diseases (SADs). The investigation of newly diagnosed drug-naive SAD patients might contribute to identify novel disease-specific and prognostic markers. The multiplex analysis of 30 plasma proteins in 60 newly diagnosed drug-naive SADs, such as RA (rheumatoid arthritis, n = 31 ), SLE (systemic lupus erythematosus, n = 19 ), and SSc (systemic scleroderma, n = 10 ) patients, versus healthy controls (HCs, n = 40 ) was addressed. Thirty plasma cytokines were quantified using the Procarta Plex™ panel. The higher expression of IL-12p40, IL-10, IL-13, IFN-γ, M-CSF, IL-4, NTproBNP, IL-17A, BMP-9, PYY (3-36), GITRL, MMP-12, and TNFRSF6 was associated with RA; IL-12p40, M-CSF, IL-4, GITRL, and NTproBNP were higher in SLE; or NTproBNP, PYY (3-36), and MMP-12 were increased in SSc over HCs, respectively. The cleaved peptide tyrosine tyrosine (PYY 3-36) was elevated in RA ( 361.6 ± 47.7 pg/ml) vs. HCs ( 163.96 ± 14.5 pg/ml, mean ± SEM , ∗ ∗ ∗ p = 4 × 10 − 5 ). The CI (95%) was 268.05-455.16 pg/ml for RA vs. 135.55-192.37 pg/ml for HCs. The elevated PYY (3-36) level correlated significantly with the increased IL-4 or GITRL concentration but not with the clinical scores (DAS28, CRP, ESR, RF, aMCV). We are the first to report cleaved PYY (3-36) as a specific plasma marker of therapy-naive RA. Additionally, the multiplex plasma protein analysis supported a disease-specific cytokine pattern in RA, SLE, and SSc, respectively.

show abstract

“…GITR is a member of the tumor necrosis factor receptor (TNFR) family highly expressed on T regulatory (Treg) cells and present on effector T lymphocytes, natural killer cells, and neutrophils [ 63 , 64 ]. GITR is activated by its ligand, GITRL, mainly expressed on antigen-presenting and endothelial cells [ 65 ]. GITR activation on effector T cells generates a positive costimulatory signal and promotes T cell activation and proliferation; however, the activation of GITR on Treg cells abolishes their suppressive function in cancer settings [ 66 ].…”

Section: Metabolic Effects Of Stimulatory Immune Checkpoint Protein Activation On Immune Cellsmentioning

confidence: 99%

Metabolic Implications of Immune Checkpoint Proteins in Cancer

Stirling

Bronson

Mackert

et al. 2022

Cells

View full text Add to dashboard Cite

Expression of immune checkpoint proteins restrict immunosurveillance in the tumor microenvironment; thus, FDA-approved checkpoint inhibitor drugs, specifically PD-1/PD-L1 and CTLA-4 inhibitors, promote a cytotoxic antitumor immune response. Aside from inflammatory signaling, immune checkpoint proteins invoke metabolic reprogramming that affects immune cell function, autonomous cancer cell bioenergetics, and patient response. Therefore, this review will focus on the metabolic alterations in immune and cancer cells regulated by currently approved immune checkpoint target proteins and the effect of costimulatory receptor signaling on immunometabolism. Additionally, we explore how diet and the microbiome impact immune checkpoint blockade therapy response. The metabolic reprogramming caused by targeting these proteins is essential in understanding immune-related adverse events and therapeutic resistance. This can provide valuable information for potential biomarkers or combination therapy strategies targeting metabolic pathways with immune checkpoint blockade to enhance patient response.

show abstract

The Role of GITR/GITRL Interaction in Autoimmune Diseases

Cited by 54 publications

References 64 publications

The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses

The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses

Investigation of Newly Diagnosed Drug-Naive Patients with Systemic Autoimmune Diseases Revealed the Cleaved Peptide Tyrosine Tyrosine (PYY 3-36) as a Specific Plasma Biomarker of Rheumatoid Arthritis

Metabolic Implications of Immune Checkpoint Proteins in Cancer

Contact Info

Product

Resources

About